Time-dependent effects of waterborne copper exposure influencing hepatic lipid deposition and metabolism in javelin goby Synechogobius hasta and their mechanism

• On day 30, Cu increased lipid content by elevating lipogenesis and reducing lipolysis.
• On day 60, Cu reduced lipid content by reducing lipogenesis and elevating lipolysis.
• Time-course change of lipid deposition and metabolism induced by Cu was obtained.
• Mechanism of Cu affecting lipid metabolism was demonstrated on enzyme and molecular levels.

The present study was conducted to determine the time-course of waterborne chronic copper (Cu) exposure effects influencing hepatic lipid deposition and metabolism in javelin goby Synechogobius hasta and their mechanisms. S. hasta were exposed to four waterborne Cu concentrations (2 (control), 18, 38 and 55 μg Cu/l) for 60 days. Sampling occurred on day 30 and day 60, respectively. Survival decreased and hepatic Cu content increased with increasing Cu levels. On day 30, Cu exposure increased hepatic lipid content, viscerosomatic index (VSI) and hepatosomatic index (HSI), and activities of lipogenic enzymes (6PGD, G6PD, ME, ICDH and FAS) as well as the mRNA levels of 6PGD, G6PD, ME, FAS, ACCα, LPL, PPARγ and SREBP-1 in the liver. However, the mRNA levels of ATGL, HSL and PPARα declined following Cu exposure. On day 60, Cu exposure reduced hepatic lipid content, HSI, VSI, activities of G6PD, ME, ICDH and FAS, and the mRNA expression of 6PGD, G6PD, ME, FAS and SREBP-1, but increased mRNA expression of CPT 1, HSL and PPARα. The differential Pearson correlation between transcriptional changes of genes encoding transcription factors (PPARα, PPARγ and SREBP-1), and the activities and mRNA expression of enzymes involved in lipogenesis and lipolysis were observed on day 30 and day 60, respectively. Cu exposure for 30 days induced hepatic lipid accumulation by stimulating lipogenesis and inhibiting lipolysis. However, 60-day Cu exposure reduced hepatic lipid content by inhibiting lipogenesis and stimulating lipolysis. To our knowledge, for the first time, the present study provided experimental evidence that waterborne chronic Cu exposure differentially influenced genes involved in lipogenic and lipolytic metabolic pathway and the enzymes encoded in a duration-dependent manner in fish, and provided new insight into the relationship between metal toxicity and lipid metabolism.